Open Label Study of BAY1082439 in Patients With Advanced Cancer

Recruitment & Eligibility

Inclusion Criteria

Subjects with advanced, histologically or cytologically confirmed solid tumors, refractory to any standard therapy, have no standard therapy available, or subjects must have actively refused any treatment which would be regarded standard, and / or if in the judgment of the investigator, experimental treatment is clinically and ethically acceptable
- Expansion phase only: Subjects with histologically or cytologically confirmed, locally advanced or metastatic endometrial cancer or breast cancer or iNHL, who are refractory to or have exhausted all available therapies
International normalized ratio (INR) and partial thromboplastin time (PTT) <1.5 x ULN [Subjects on anticoagulation with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.] For subjects on warfarin, close monitoring of at least weekly evaluations will be performed until INR is stable based on a measurement at pre-dose, as defined by the local standard of care
Measurable or evaluable disease
Life expectancy of at least 12 weeks
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Adequate bone marrow, liver and renal function

Exclusion Criteria

History of cardiac disease: congestive heart failure > New York Heart Association (NYHA) Class II, unstable angina (anginal symptoms at rest), new-onset angina (within the past 3 months prior to the first dose of study drug), myocardial infarction within the past 6 months prior to the first dose of study drug, or cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management
History of diabetes mellitus or gestational diabetes mellitus
Fasting blood glucose level >125 mg/dL or HbA1c 7% at screening
Active clinically serious infections > Grade 2
History of organ allograft
Seizure disorder requiring therapy (such as steroids or anti-epileptics)

Study & Design

Arm && Interventions

Group	Intervention	Description
Arm 1	BAY1082439	-

Primary Outcome Measures

Name	Time	Method
Number of participants with adverse events as a measure of safety and tolerability	Up to 2 years
Maximum tolerated dose of BAY1082439	Up to 1 year
Maximum observed plasma concentration (Cmax) of BAY1082439 after a single dose	Serial PK samples will be selected during cycle 1 day 1 (pre-dose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose) and sparse samples during the rest of the cycle as well as in cycle 2
Time to Cmax (tmax) of BAY1082439 after a single dose	Serial PK samples will be selected during cycle 1 day 1 (pre-dose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose) and sparse samples during the rest of the cycle as well as in cycle 2
Area under the plasma concentration-time curve (AUC[0-t]) of BAY1082439 after a single dose	Serial PK samples will be selected during cycle 1 day 1 (pre-dose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose) and sparse samples during the rest of the cycle as well as in cycle 2

Secondary Outcome Measures

Name	Time	Method
Area under the concentration-time curve over the dosing interval (AUC[0-tau])	PK parameters following single and repeat-dose administration in cycle 1
Maximum observed concentration (Cmax)	PK parameters following single and repeat-dose administration in cycle 1
Time of occurrence of Cmax (tmax)	PK parameters following single and repeat-dose administration in cycle 1
Terminal phase half-life (t1/2)	PK parameters following single and repeat-dose administration in cycle 1
Tumor response based on Response Evaluation Criteria in Solid Tumors, Version 1.1	Up to 2 years

Recruitment & Eligibility